1. Field of the Invention
This invention relates to a method for resetting the phase of the human circadian clock and for enhancing alertness and performance in humans by application of non-solar photic stimulation, in the range of 15 to 150,000 lux, to any non-ocular region of the human body.
2. Related Art
As with all vertebrates, humans exhibit temporal organization in behavior and in numerous physiological functions. In response to the natural alternation in light and dark, virtually all species have developed endogenous rhythms with frequencies close to 24 hours. These internally generated, self-sustaining rhythms are known as circadian rhythms (from the Latin circa =about, and dies =day). The pervasive nature of such rhythms suggests that circadian temporal organization is vital to the overall well-being of the organism. Numerous systems and functions are mediated by the circadian system including hormonal output, body temperature, rest and activity, sleep and wakefulness, and motor and cognitive performance. In all, literally hundreds of circadian rhythms in mammalian species have been identified.
Left to run at its inherent frequency, the human biological clock that is responsible for the generation of circadian rhythms exhibits a daily periodicity of slightly longer than 24 hours. Thus, a daily correction to the clock must be made for our internal rhythms to remain synchronized or `entrained` to the natural 24 hour day. It is widely accepted that exposure to the natural light/dark cycle provides the strongest signal to entrain the human circadian system to the geophysical day. Inadequate exposure to light of sufficient intensity is a contributing factor in disorders associated with biological rhythm disturbance, such as seasonal affective disorder (SAD), jet lag from transmeridian travel, shift work and some types of insomnia (advanced and delayed sleep phase syndromes). Timed exposure to artificial bright light to the eyes has been used successfully to treat such disorders. Some examples of studies relating to the effects of timed ocular exposure to artificial bright light are discussed in U.S. Pat. Nos. 5,167,228 and 5,176,133 to Czeisler, which are herein incorporated by reference.
There is compelling evidence that bright ambient illumination on the eyes can have an immediate, acute enhancing effect on alertness and performance. By way of example, the article entitled, "Enhancement of Nighttime Alertness and Performance with Bright Ambient Light" by Scott S. Campbell and Drew Dawson in Physiology & Behavior Vol. 48, pp. 317-320, 1990, demonstrates that ocular exposure to illumination of about 1,000 lux enhances a human's alertness and performance. This non-circadian property of light exposure is of particular relevance to people who must work night or rotating shift work schedules, since declines in alertness and performance may result in increased accident rates, reduced productivity and increased health care costs.
It is widely accepted that the mammalian circadian clock which is located in the brain, within the suprachiasmatic nuclei (SCN) of the hypothalamus, receives photic information via the eyes, by visual and/or non-visual ocular pathways originating in the retina. It is also widely acknowledged that light acts to enhance alertness and performance via an ocular route(s). Yet, it has been recognized for decades that many species of birds and reptiles possess extra-ocular photoreceptors, and it has been demonstrated that circadian and photoperiodic response to light can be mediated entirely by such photoreceptors. In contrast, it is generally assumed that such nonvisual circadian photoreceptors in mammals reside within the retina, and that mammals do not possess the capacity for extraocular circadian photoreception. This conclusion is based on studies showing a failure of several rodent species to entrain to a light/dark cycle, or to respond to pulses of light with shifts in circadian phase, following complete optic enucleation.
Perhaps because of the widespread acceptance of the notion that mammals have no capacity for extraocular circadian photoreception, only two studies have examined whether extraocular light exposure can impact brain functioning in humans. In a study of blind subjects, Czeisler and coworkers found an absence of light-induced melatonin suppression during ocular shielding in two individuals who did show melatonin suppression when light fell on their eyes. A decade earlier, Wehr and coworkers reported a lack of clinical response in seasonal affective disorder when patients' skin (face, neck, arms and legs) was exposed to a bright light stimulus (2500 lux) while their eyes were shielded. No study has examined specifically whether circadian phase resetting can be achieved in humans via extraocular pathways.
As noted above, ocular exposure to timed bright light has been shown to be an effective remedy for circadian rhythm disorders. Unfortunately, treatment regimens involving ocular exposure to bright light are tedious and time-consuming. Many patients are simply unwilling or unable to remain relatively stationary for extended periods gazing at a bright light stimulus.
Additionally, the nature of the phase response curve to light dictates that the largest shifts, both advances and delays, are achieved at times during which people are typically asleep. Thus, all but the most committed users of bright light treatments fail to benefit from the most efficient temporal application of the intervention. Attempts have been made to remedy these problems by the development of `light visors`, which are devices worn like a cap that are intended to permit the user more freedom of movement while receiving light exposure. In practice, such devices are likely to be poorly received since they also direct light toward the eyes, and therefore, limit the visual field.
Also, as noted above, ocular light exposure has been demonstrated to improve alertness and performance. Unfortunately, as with circadian clock resetting, the use of ocular light in this capacity has considerable drawbacks. By way of example, the implementation of bright ambient light is likely to be impractical for use in typical industrial control room settings. Rapidly increasing utilization of computer technology for monitoring and controlling plant operations calls for ambient lighting conditions that take into consideration the effects of glare and contrast on computer displays.
In summary, because light must still enter through the eyes, unrestricted vision cannot be achieved, and mobility is limited. Simply, any device that successfully gets light to the eyes, is likely to interfere with normal activities. The result is reduced compliance and limited effectiveness of light treatment interventions as currently applied.